The primary goal of this research is to understand the molecular events that underlie the process of leukemogenesis by C-type murine retroviruses (MuLVs). Specifically, the T-cell lymphomagenic virus SL3-3 (SL3) will be studied with respect to the enhancer elements within the Long Terminal Repeats. Three specific aims are proposed. 1) To define the interactions among the cellular transcription factors in T-lymphocytes that can activate the SL3 enhancer. Three factors will be focused on: CBF, c-Myb, and Ets-1. 2) Key aspects of transcriptional regulation for lymphomagenesis by SL3 will be studied. Critical elements in the SL3 enhancer will be further defined. Mutations within the enhancers will be examined to see if the affect viral replication in cultured T cells and in the lymphoid organs in mice. 3) The ability of these enhancers to activate the promoters of cellular proto-oncogenes in T-cell lymphomas will be analyzed. Specifically, the activation of c-myc and pim-1 will be studied. Additional studies will aim at identifying alternative proto-oncogenes which may be activated.